2-Bromoanisole → 3-Hydroxy-3-(2-methoxyphenyl)-5-trifluoromethoxy-1,3-dihydro-2H-indol-2-one

HRID 31352

Reaction equation

HRID 31352 reaction equation
[Mg:1].[Br:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[F:11][C:12]([F:26])([F:25])[O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18](=[O:23])[C:17]2=[O:24].[NH4+].[Cl-]>CCOCC.C1COCC1>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][CH:20]=[CH:21][C:22]=1[Mg:1][Br:2].[OH:24][C:17]1([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[O:9][CH3:10])[C:16]2[C:20](=[CH:21][CH:22]=[C:14]([O:13][C:12]([F:11])([F:25])[F:26])[CH:15]=2)[NH:19][C:18]1=[O:23]

Participants

8

Reactant 4

HCID 113582-BromoanisoleHCID 25517Ammonium ChlorideHCID 27327525-(trifluoromethoxy)-2,3-dihydro-1H-indole-2,3-dioneHCID 5462224Magnesium

Product 2

HCID 219058993-Hydroxy-3-(2-methoxyphenyl)-5-trifluoromethoxy-1,3-dihydro-2H-indol-2-oneYield 76.3%HCID 178489560HCID 178489560, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-methoxyphenylmagnesium bromide is prepared starting with 1.9 g of magnesium in 4 ml of ether and a solution of 14.54 g of 1-bromo-2-methoxybenzene in 21 ml of ether. This solution is added dropwise, under an argon atmosphere, to a mixture of 5 g of 5-trifluoromethoxy-1H-indole-2,3-dione in 26 ml of THF, precooled on an ice bath, the resulting mixture is then heated at the reflux temperature of the ether for 1 hour 30 minutes and is allowed to cool to RT. The reaction mixture is poured slowly into saturated NH4Cl solution and extracted with EtOAc, the organic phase is washed with 5% K2CO3 solution, with water and with saturated NaCl solution and dried over Na2SO4, and the solvent is evaporated off under vacuum. 2.8 g of the expected product are obtained.

Workup

  1. customprecooled on an ice bath
  2. extractionextracted with EtOAc
  3. washthe organic phase is washed with 5% K2CO3 solution, with water and with saturated NaCl solution
  4. dry with materialdried over Na2SO4
  5. customthe solvent is evaporated off under vacuum

Sources & evidence

ORD record
ord-c0c9fcda8b5943aea3d4da63af3bb7f5
Source dataset
uspto-grants-2008_09
Patent number
US07425566B2

Linked notes

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